| 1999 |
Fission yeast condensin SMC4 ortholog Cut3 is directly phosphorylated by Cdc2 kinase at T19 in vitro and in vivo (maximal in metaphase); this phosphorylation is required for nuclear accumulation of the condensin complex during mitosis, and an alanine substitution (T19A) blocks both nuclear localization and chromosome condensation. |
In vitro Cdc2 kinase assay, in vivo phosphorylation mapping, GFP localization of condensin subunits, alanine-substitution mutagenesis with temperature-sensitive suppression assay |
Genes & development |
High |
10485849
|
| 1999 |
Fission yeast condensin is a five-member complex composed of two SMC subunits (Cut3/SMC4 and Cut14/SMC2) and three non-SMC subunits (Cnd1, Cnd2, Cnd3); all five subunits are essential for mitotic chromosome condensation, and loss of any non-SMC subunit phenocopies loss of the SMC subunits. |
Complex purification, microsequencing of subunits, gene disruption and phenotypic analysis |
Genes & development |
High |
10485849
|
| 2000 |
Human SMC4 (hCAP-C) forms a heterodimeric complex with hCAP-E, and this complex co-immunoprecipitates a 155-kDa non-SMC subunit CNAP1 (homolog of Xenopus XCAP-D2), demonstrating the existence of a condensin complex in human cells; the complex is predominantly cytoplasmic in interphase and associates with mitotic chromosomes in a cell-cycle-specific manner. |
Co-immunoprecipitation from HeLa extracts, immunofluorescence/chromosome localization, sequence homology analysis |
Molecular and cellular biology |
High |
10958694
|
| 2001 |
Drosophila SMC4 (encoded by the gluon locus) localizes to the axial chromosome core at metaphase and anaphase, and loss-of-function mutations cause failure of sister chromatid resolution (not simply failure of axis shortening), leading to chromosome segregation defects, chromosome breakage, and apoptosis. |
Genetic mutant analysis (hypomorphic/null gluon alleles), immunofluorescence of DmSMC4 during mitosis, cytological analysis of mitotic chromosome structure |
Current biology : CB |
High |
11267866
|
| 2015 |
Cross-linking mass spectrometry combined with molecular modelling of the chicken condensin SMC2/SMC4 dimer revealed that the two subunits' anti-parallel coiled-coils can adopt a closely apposed configuration, and that both histone H2A and H4 may contact condensin in situ on mitotic chromosomes. |
Amino acid-selective chemical cross-linking, mass spectrometry, homology-based molecular modelling |
Open biology |
Medium |
25716199
|
| 2016 |
AFM imaging of S. cerevisiae Smc2-Smc4 dimers showed that the coiled-coil arms are highly flexible (persistence length ~4 nm), can adopt multiple architectures interconverting over time, and that the SMC head domains engage not only each other but also the hinge domain at the opposite end of the ~45-nm coiled coil. |
High-speed atomic force microscopy (AFM) in liquid |
Cell reports |
High |
26904946
|
| 2018 |
SMC4 (Smc4) promotes inflammatory innate immune responses by recruiting H4K5 acetyltransferase activity to the NEMO promoter, increasing H4K5 acetylation and thereby enhancing NEMO transcription; elevated NEMO then potentiates NF-κB and IRF3 activation. Smc4 knockdown in macrophages reduced TLR/virus-triggered IL-6, TNF-α, and IFN-β production, and mice with Smc4 knockdown were less susceptible to sepsis. |
High-throughput epigenetic modifier screen, siRNA/shRNA knockdown, ChIP for H4K5ac at NEMO promoter, cytokine measurement by ELISA, in vivo sepsis model |
Journal of autoimmunity |
Medium |
29803706
|
| 2019 |
Condensin core subunits Smc2 and Smc4 in budding yeast are regulated at the level of protein stability in a cell-cycle-dependent manner, peaking at mitosis and falling in interphase; Smc4 degradation at mitotic exit is dependent on the APC/C and mediated by the proteasome. Unexpectedly, the spindle checkpoint protein Mad2 is required for mitotic Smc4 degradation. Overproduction of Smc4 delays decondensation but has limited ability to promote premature condensation. |
Protein abundance western blotting across cell cycle, APC/C mutant epistasis, proteasome inhibitor treatment, MAD2 deletion analysis, Smc4 overexpression phenotypic analysis |
Oncotarget |
Medium |
30719224
|
| 2023 |
SMC4 acts as a transcriptional co-activator of PGAM1; SMC4 attenuation suppresses PGAM1 expression, and coordinated loss of both SMC4 and PGAM1 disrupts F-actin assembly, causing cytokinesis failure and polyploidy. Additionally, SMC4 attenuation upregulates three glycolysis investment-phase enzymes increasing lactate, which drives histone lactylation-mediated ABC transporter upregulation, rendering cells chemotherapy-insensitive (diapause-like state). |
SMC4 knockdown experiments, reporter/ChIP assays for PGAM1 transcription co-activation, F-actin staining, flow cytometry for ploidy, metabolic flux assays, histone lactylation analysis |
Cell metabolism |
Medium |
37543034
|
| 2020 |
In Plasmodium, SMC2 and SMC4 core subunits localize to centromeres during early schizogony (confirmed by NDC80 colocalization and ChIP-seq) without forming condensin I or II complexes, but in mature schizonts and male gametogenesis they distribute diffusely on chromosomes and form both condensin I and condensin II complexes. |
Fluorescence imaging with NDC80 marker, ChIP-seq for centromere localization, immunoprecipitation to detect condensin I/II complex formation, conditional knockdown |
Cell reports |
High |
32049018
|
| 2025 |
SMC4 interacts with GLUT1 (encoded by Slc2a1) as revealed by IP-MS, and this interaction is confirmed by co-IP; SMC4 knockdown inhibits glycolysis rate, ATP production, and mTOR/Rheb activation, reducing prostate cancer cell proliferation and lung metastasis in vivo. |
IP-MS (interactome), co-immunoprecipitation, CRISPR/Cas9 SMC4 knockdown, glycolytic rate assay, RNA-seq KEGG pathway analysis, murine lung metastasis model |
Advanced science |
Medium |
40278414
|
| 2025 |
SMC4 maintains genomic stability to suppress cGAS-STING-mediated type I interferon production in triple-negative breast cancer cells, and independently upregulates PD-L1 expression through a STING-independent mechanism, enabling immune evasion from CD8+ T cells. |
SMC4 knockdown/overexpression cell lines, western blot/RT-qPCR/ELISA for IFN and PD-L1, molecular docking, immunoprecipitation, CD8+ T cell co-culture assays, in vivo 4T1 immunocompetent murine model |
International immunopharmacology |
Medium |
40976049
|
| 2024 |
FoxO1 promotes SMC4 transcription by binding to the SMC4 promoter at the -1400/-1390 bp region (confirmed by ChIP-seq), and also transcriptionally activates METTL14, which increases m6A methylation on SMC4 mRNA coding sequence, enhancing SMC4 mRNA abundance in ovarian cancer cells. |
ChIP-seq, dual-luciferase reporter assay, FoxO1 knockdown, METTL14 knockdown, m6A methylation analysis, in vitro and in vivo proliferation assays |
Cancer science |
Medium |
38403332
|
| 2024 |
ZNF131 transcriptionally activates SMC4 expression in hepatocellular carcinoma by binding the SMC4 promoter through interaction with ZBTB33 (ChIP-qPCR and dual-luciferase reporter); enforced SMC4 overexpression partially rescues the tumor-suppressive effects of ZNF131 knockdown. |
ChIP-qPCR, dual-luciferase reporter assay, ZNF131 knockdown, SMC4 overexpression rescue experiment, xenograft tumor models |
Biochemical and biophysical research communications |
Medium |
38241815
|
| 2025 |
SMC4 promotes myeloma cell growth by epigenetically enhancing IFI16-STING signaling, leading to increased pro-inflammatory cytokine production that creates a favorable microenvironment; pharmacological inhibition of the IFI16-STING pathway abrogates the oncogenic effects of SMC4. |
SMC4 depletion (proliferation and clonogenicity assays), epigenetic pathway analysis, IFI16/STING pathway inhibition experiments |
Apoptosis |
Low |
41793503
|
| 2025 |
SMC4 in cervical cancer upregulates SMAD3 and activates NF-κB signaling, promoting PD-L1 expression; SMC4 knockdown under ionizing radiation impairs DNA damage repair, reduces S-phase cells, and sensitizes cells to radiation. |
SMC4 knockdown, immunofluorescence for DNA damage markers, cell-cycle analysis, colony formation under ionizing radiation, western blot for SMAD3/NF-κB/PD-L1 |
Journal of translational medicine |
Low |
41803949
|
| 2025 |
NFIA directly binds two motifs in the SMC4 promoter (-1379 bp and -354 bp) to drive SMC4 transcription in glioma, as confirmed by dual-luciferase reporter and ChIP assays; SMC4 in turn promotes TGF-β/SMAD signaling (upregulating p-SMAD2/3, N-cadherin, SNAI1, ZEB1) and aerobic glycolysis via LDHA upregulation. |
ChIP assay, dual-luciferase reporter, SMC4 knockdown/overexpression, LDHA rescue experiments, ECAR/OCR metabolic assays, in vivo xenograft and metastasis models |
Frontiers in oncology |
Medium |
40933894
|
| 2025 |
SMC4 is identified as a potential substrate of Polo-like kinase 1 (Plk1) in mitosis; Plk1 inhibition leads to downregulation of nascent transcription and reduced chromosomal accessibility, with SMC4 as a common subunit of condensin I and II implicated in mediating these effects. |
5-EU labeling of nascent RNA, Plk1 inhibitor treatment, chromatin accessibility profiling (ATAC-seq implied), substrate identification (method not fully specified in abstract) |
bioRxivpreprint |
Low |
|
| 2025 |
AFM imaging of yeast condensin revealed that head engagement upon ATP binding is coupled to hinge opening in the Smc2/Smc4 heterodimer, and that after ADP release the N-terminal region of the non-SMC subunit Brn1 re-associates with the Smc2 head domain. |
Solution AFM imaging with varying nucleotides (AMP-PNP, ATPγS, ADP), coarse-grained molecular dynamics simulations, flexible molecular fitting |
bioRxivpreprint |
Medium |
|
| 2026 |
Tumor cell-derived exosomal E2F7 is transferred to macrophages where it binds SMC4 to induce M2-like macrophage polarization, promoting an immunosuppressive tumor microenvironment in colorectal cancer. |
Exosome isolation by ultracentrifugation, co-immunoprecipitation of E2F7 and SMC4, in vitro macrophage polarization assay, in vivo CRC mouse model |
International immunopharmacology |
Low |
42119232
|
| 2022 |
TREM-1 interacts with SMC4 in cardiomyocytes (identified by co-immunoprecipitation); inhibition of either TREM-1 or SMC4 prevented NLRP3 inflammasome upregulation and decreased Gasdermin-D, IL-1β, and caspase-1 cleavage, indicating SMC4 functions downstream of TREM-1 in the pyroptosis pathway in sepsis. |
Co-immunoprecipitation, SMC4 siRNA knockdown, TREM-1 inhibitor (LR12), NLRP3 inflammasome activation assay, in vivo cecal ligation and puncture model |
The FEBS journal |
Low |
36181338
|